Unresectable or Metastatic Hepatocellular CarcinomaPhase 2GDFATHERHCC01NCT07219459
Visugromab, Nivolumab and Lenvatinib Compared to Double Placebo and Lenvatinib in Unresectable or Metastatic Hepatocellular Carcinoma Post Anti-PD-(L)1 Failure
A Phase 2 study testing Visugromab RDE (recommended dose for expansion), Nivolumab and Lenvatinib in people with Unresectable or Metastatic Hepatocellular Carcinoma and Child-Pugh A Hepatocellular Carcinoma, run by CatalYm GmbH at 23 sites in 6 countries.
Trial summary
This is a Phase 2b, randomized, blinded clinical trial investigating the efficacy and safety of visugromab in combination with nivolumab and Lenvatinib compared to double placebo and Lenvatinib in participants with unresectable or metastatic HCC and compensated liver function (Child-Pugh A) after failure of 1L… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Unresectable or Metastatic Hepatocellular Carcinoma, Child-Pugh A Hepatocellular Carcinoma, Failure of First-Line Treatment That Included an Approved Anti PD-(L)1 Compound
- What is being tested?
- Visugromab RDE (recommended dose for expansion), Nivolumab and Lenvatinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 104 participants
- Where
- 23 sitesin 6 countries
- Study dates
- 19 Mar 2026to Sep 2031
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Main Inclusion Criteria:
- Histologically confirmed diagnosis of unresectable or metastatic HCC, not amenable to a curative treatment approach.
- Measurable disease as per RECIST v1.1 as determined by the Investigator based upon local radiologist assessment.
- Must have failed one line of prior systemic treatment for unresectable or metastatic HCC containing an approved anti PD (L)-1 checkpoint inhibitor (CPI) with a minimum treatment duration of 12 weeks exposure for the CPI with no documented progression in this period.
- Age ≥ 18 years on the day of signing the informed consent.
- Life expectancy of at least 3 months as assessed by the Investigator.
- ECOG performance status ≤1.
- Child-Pugh score of A6 or better.
Main Exclusion Criteria:
- Known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma.
- More than 1 line of prior systemic treatment for unresectable or metastatic HCC.
- Received or completed any palliative radiotherapy for symptoms within 28 days of the first dose of IMP.
- Expected to require any other form of antineoplastic therapy during the trial.
- Clinically active inflammatory bowel disease, active diverticulitis, intra-abdominal abscess, and/or gastrointestinal obstruction.
- Known history of other prior malignancy unless participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
- Known or detected clinically active central nervous system (CNS) involvement by HCC or other tumors.
- Have one of the following cardiovascular risk factors: myocardial infarction, peri/myocarditis, or history of ischemic stroke in the past 3 months before planned treatment start, uncontrolled heart failure, uncontrolled ventricular arrhythmia, QT interval corrected for heart rate using Fridericia's formula interval ≥ 470 ms regardless of sex.
- An active autoimmune disease that has required systemic treatment in past 3 months before planned treatment start.
- Comedication with metformin or metformin-containing antidiabetics in participants with type II diabetes.
- Chronic systemic corticosteroid treatment for other reasons.
- Prior liver or other organ transplantation.
Trial locations and contacts
23 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
23 sites in 6 countries
United States6 sites, 6 recruiting
- Recruiting
Peidmont Healthcare, Inc
Atlanta, Georgia, 30309
Sope Olugbile, MD, 404 (425) 1777, sope.olugbile@piedmont.org
Karma MCcants, 404 (605) 2366, karma.mccants@piedmont.org
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Ilyas Sahin, Dr, 617-724-4000, isahin@mgh.harvard.edu
- Recruiting
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612
Farshid Dayyani, Dr, (714) 456-5153, fdayyani@hs.uci.edu
Jacqueline Cedeno, (714) 456-5153, cedenoj@hs.uci.edu
- Recruiting
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Anthony El-Khoueiry, Dr, +1 (323) 865 3000, elkhouei@med.usc.edu
Charlean Ketchens, +1 (323) 865 3000, ketchens_c@med.usc.edu
- Recruiting
UC Irvine Health. Chao Family Comprehensive Cancer Center
Orange, California, 92868
Farshid Dayyani, Dr, (714) 456-5153, fdayyani@hs.uci.edu
Jacqueline Cedeno, (714) 456-5153, cedenoj@hs.uci.edu
- Recruiting
OSF St. Francis Medical Center
Peoria, Illinois, 61637
Robert McWilliams, Dr., (309)308-3800, Robert.R.McWilliams@osfhealthcare.org
Peyton Swearingen, Peyton.O.Swearingen@osfhealthcare.org
Spain5 sites, 5 recruiting
- Recruiting
Hospital Clinic of Barcelona
Barcelona, Catalonia, 08036
María Reig, Dr, +34 932279235, MREIG1@clinic.cat
- Recruiting
Catalan Institute of Oncology, Hospital Duran i Reynals
L'Hospitalet de Llobregat, Barcelona, 08908
Mariona Calvo Campos, Dr, +34932607744, mcalvo@iconcologia.net
Maria Sellés Altés, Dr, +34 (678) 004-888, mselles@idibell.cat
- Recruiting
University Hospital Ramon y Cajal
Madrid, Madrid, 28034
José Luis Lledó Navarro, +34 913368592, jllledo63@yahoo.es
- Recruiting
University Clinic of Navarra - Pamplona
Pamplona, Chartered Community of Navarra, 31008
Bruno Sangro Gomez-Acebo, +34 932607744, bsangro@unav.es
- Recruiting
University Hospital Miguel Servet
Zaragoza, Aragon, 50009
Roberto Pazo Cid, Dr., +34 (976) 765 500, rpazo@salud.aragon.es
Italy4 sites, 4 recruiting
- Recruiting
Polyclinic S. Orsola-Malpighi
Bologna, 40138
Fabio Piscaglia, MD, +39 0512142477, fabio.piscaglia@unibo.it
- Recruiting
Ospedale San Raffale, IRCCS
Milan, 20132
Andrea Casadei Gardini, MD, +39 0226438142, CasadeiGardini.Andrea@hsr.it
- Recruiting
Asst Grande Ospedale Metropolitano Niguarda
Milan, 20162
Katia Bencardino, Dr., +390264442291, oncologia@ospedaleniguarda.it
- Recruiting
Ospedale S.Maria delle Croci
Ravenna, 48121
Stefano Tamberi, Dr., +390544285891, stefano.tamberi@auslromagna.it
France3 sites, 3 recruiting
- Recruiting
Centre Hospitalier Universitaire de Bordeaux - Hôpital Haut-Lévêque
Pessac, 33604
Jean-Frederic Blanc, Dr, +33 (5) 57 65 64 39, jean-frederic.blanc@chu-bordeaux.fr
- Recruiting
Poitiers University Hospital Center - Miletrie Hospital
Poitiers, 86000
Amina Larbi Bouamrane, Dr, +33 (549) 444 444, amina.larbi-bouamrane@chu-poitiers.fr
- Recruiting
Gustave Roussy
Villejuif, 94805
Valerie Boige, Dr, +33 (142) 115-799, valerie.boige@gustaveroussy.fr
Germany3 sites, 3 recruiting
- Recruiting
Universitätsklinikum Frankfurt Johann Wolfgang Goethe- Universität
Frankfurt, 60590
Jörg Trojan, Prof., +4969630187769, trojan@em.uni-frankfurt.de
- Recruiting
Hannover Medical School
Hanover, Lower Saxony, 30625
Anna Saborowski, PD Dr. med., +495115329592, Saborowski.Anna@mh-hannover.de
- Recruiting
University Medical Center of Johannes Gutenberg University Mainz
Mainz, Rhineland-Palatinate, 55131
Peter R. Galle, Prof. Dr. med., +49 (0) 6131 17 7276, galle@uni-mainz.de
United Kingdom2 sites, 2 recruiting
- Recruiting
Western General Hospital
Edinburgh, EH4 2XU
Mary Carson, 0131 5372669, Mary.Carson@nhs.scot
- Recruiting
King's College Hospital
London, SE5 9RS
Debashis Sarker, Dr, 020 3299 7615, debashis.sarker1@nhs.net
About this study
Official title: A Phase 2b, Randomized, Blinded Trial Investigating the Efficacy and Safety of Visugromab in Combination With Nivolumab and Lenvatinib Compared to Double Placebo and Lenvatinib in Participants With Unresectable or Metastatic Hepatocellular Carcinoma and Compensated Liver Function (Child-Pugh A) After Failure of First-Line Treatment That Included an Approved Anti PD-(L)1 Compound (GDFATHER HCC-01)
This is a Phase 2b, randomized, blinded clinical trial investigating the efficacy and safety of visugromab in combination with nivolumab and Lenvatinib compared to double placebo and Lenvatinib in participants with unresectable or metastatic HCC and compensated liver function (Child-Pugh A) after failure of 1L treatment that included an anti-PD-(L)1 compound. The trial consists of 2 Parts: a non-randomized Safety-run-in part (Part 1) and the subsequent randomized part (Part 2) with 2 treatment arms (A and B). Randomization of participants into Treatment Arm A and B will continue until 40 efficacy-evaluable participants are enrolled into each Treatment Arm.
- Conditions
- Unresectable or Metastatic Hepatocellular Carcinoma, Child-Pugh A Hepatocellular Carcinoma, Failure of First-Line Treatment That Included an Approved Anti PD-(L)1 Compound
- Being tested
- Visugromab RDE (recommended dose for expansion), Nivolumab, Lenvatinib, Placebo Saline Infusion
- Keywords
- CTL-002, Visugromab, GDF-15
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Visugromab RDE (recommended dose for expansion)Biological
Also called CTL-002
Participants receive visugromab (RDE) intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments
NivolumabBiological
Also called OPDIVO®
Participants receive Nivolumab 360mg intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments after visugromab infusion
LenvatinibDrug
Also called Lenvima
Participants receive Lenvatinib per os (PO) once daily according to body weight (> 60kg: 12mg; < 60kg: 8mg)
Placebo Saline InfusionOther
Also called 0.9% NaCl
Saline (0.9%NaCl) intravenous (2x IV) on Day 1 of every 21-day cycle every 3 weeks (Q3W) for up to 35 treatments
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Visugromab (IV) + Nivolumab intravenous (IV) + Lenvatinib (PO) Receives: Biological: Visugromab RDE (recommended dose for expansion); Biological: Nivolumab; Drug: Lenvatinib |
| Arm B | Active comparator | Lenvatinib (PO) + saline (double-placebo) intravenous (IV) Receives: Drug: Lenvatinib; Other: Placebo Saline Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS)
Investigator assessed Progression-free survival (PFS) time from randomization (during Safety Run-In: initiation of treatment) to first documented disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurred first.
Measured: up to 36 months
Secondary outcomes (10)
Independently assessed PFS by Blinded Independent Central Review (BICR)
Measured: up to 36 months
CR (Complete Response) rate
Measured: up to 36 months
PR (Partial Response) rate
Measured: up to 36 months
ORR (Overall Response) rate
Overall response rate, defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) per RECIST v1.1 as assessed by the Investigator
Measured: up to 36 months
TTR (Time-to-response) rate
Measured: up to 36 months
PFS (Progression-free survival) rate
Measured: up to 36 months
Change in body weight (kg) from baseline
Measured: up to 39 months
Adverse Events
Incidence, type and severity of adverse events, treatment emergent adverse events, treatment-related adverse events and serious adverse events
Measured: up to 60 months
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score [0-100]
Assess participants' subjective wellbeing; higher score means better Quality of Life
Measured: up to 39 months
Overall survival (OS)
Measured: up to 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2025
- Study start19 Mar 2026
- Primary completionSep 2029 (estimated)
- Study completionSep 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unresectable or Metastatic Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 104 participants (estimated)
Sponsor and investigators
- Lead sponsor
- CatalYm GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07219459
- Sponsor's protocol ID
- CTL-002-005
- Other IDs
- 2025-520675-86-00, 2025
- Acronym
- GDFATHERHCC01
- Status last verified
- Sep 2026
- First submitted
- 20 Oct 2025
- Last updated
- 23 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No